Pharmaceutical composition of MEK inhibitor and preparation method thereof

Abstract

The present application provides a pharmaceutical composition comprising 6-(2-chloro-4-iodophenylamino)-N-(2-hydroxyethoxy)-5-methyl-4-oxo-4,5-dihydrofuro[3,2-c]pyridine-7-carboxamide or a pharmaceutically acceptable salt, a binder, a surface stabilizer and a dispersant, wherein the pharmaceutical composition can be dispersed in water to form a pharmaceutical suspension having a median particle size, X50, of 0.5 μm to 4.0 μm. Also disclosed are a preparation method thereof and the use thereof for treating cancers.

What is claimed is: 
     
       1. A pharmaceutical composition, comprising 6-(2-chloro-4-iodophenylamino)-N-(2-hydroxyethoxy)-5-methyl-4-oxo-4,5-dihydrofuro[3,2-c]pyridine-7-carboxamide or a pharmaceutically acceptable salt thereof, a binder, a surface stabilizer, and a dispersant, wherein the pharmaceutical composition can be dispersed in water to form a pharmaceutical suspension having a median particle size, X50, of 0.5 μm-4.0 μm. 
     
     
       2. The pharmaceutical composition according to  claim 1 , wherein the binder is selected from the group consisting of starch paste, methylcellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose, sodium carboxymethylcellulose, ethylcellulose, polyvinylpyrrolidone, polyethylene glycol, and any mixture thereof. 
     
     
       3. The pharmaceutical composition according to  claim 1 , wherein the surface stabilizer is selected from the group consisting of sodium dodecyl sulfate, glycerol, syrup, a water-soluble macromolecule compound, and any mixture thereof. 
     
     
       4. The pharmaceutical composition according to  claim 3 , wherein the water-soluble macromolecule compound is selected from the group consisting of acacia, tragacanth, peach gum, methylcellulose, sodium carboxymethylcellulose, hydroxypropylcellulose, carbopols, polyvinylpyrrolidone, dextran, and any mixture thereof. 
     
     
       5. The pharmaceutical composition according to  claim 1 , wherein the dispersant is selected from the group consisting of sucrose, maltose, fructose, glucose, lactose, glycerol, sorbose, xylitol, mannitol, stevioside, saccharin sodium, aspartame, and any mixture thereof. 
     
     
       6. The pharmaceutical composition according to  claim 1 , wherein the pharmaceutical composition can be dispersed in water to form the pharmaceutical suspension having a median particle size, X50, of 1.0 μm-3.0 μm. 
     
     
       7. The pharmaceutical composition according to  claim 1 , wherein the pharmaceutical composition further comprises blank cores, and the blank cores are selected from the group consisting of microcrystalline cellulose cores, amylose cores, and lactose cores. 
     
     
       8. The pharmaceutical composition according to  claim 7 , wherein the blank cores account for from 60 wt %-98 wt % of the total mass of the pharmaceutical composition. 
     
     
       9. The pharmaceutical composition according to  claim 7 , wherein the 6-(2-chloro-4-iodophenylamino)-N-(2-hydroxyethoxy)-5-methyl-4-oxo-4,5-dihydrofuro[3,2-c]pyridine-7-carboxamide or a pharmaceutically acceptable salt thereof accounts for from 0.5 wt %-15 wt % of the pharmaceutical composition. 
     
     
       10. The pharmaceutical composition according to  claim 7 , wherein the binder accounts for from 0.25 wt %-15 wt % of the total mass of the pharmaceutical composition. 
     
     
       11. The pharmaceutical composition according to  claim 7 , wherein the surface stabilizer accounts for from 0.02 wt %-15 wt % of the total mass of the pharmaceutical composition. 
     
     
       12. The pharmaceutical composition according to  claim 7 , wherein the dispersant accounts for from 0.5 wt %-30 wt % of the total mass of the pharmaceutical composition. 
     
     
       13. The pharmaceutical composition according to  claim 7 , wherein the pharmaceutical composition is pellets comprising a microcrystalline cellulose core and an outer layer surrounding the microcrystalline cellulose core and comprising 6-(2-chloro-4-iodophenylamino)-N-(2-hydroxyethoxy)-5-methyl-4-oxo-4,5-dihydrofuro[3,2-c]pyridine-7-carboxamide or a pharmaceutically acceptable salt thereof, hydroxypropylcellulose, sodium dodecyl sulfate, and sucrose. 
     
     
       14. The pharmaceutical composition according to  claim 13 , wherein the outer layer is coated with a coating comprising a film-forming agent and/or a plasticizer and/or a pigment. 
     
     
       15. The pharmaceutical composition according to  claim 1 , further comprising a filler, a disintegrant, a lubricant, an adhesive, a plasticizer, a film coating premix and/or a capsule shell. 
     
     
       16. The pharmaceutical composition according to  claim 15 , wherein the pharmaceutical composition is in the form of granules, tablets, pills or capsules. 
     
     
       17. A granule, tablet, pill or capsule comprising the pharmaceutical composition according to  claim 1 . 
     
     
       18. The pharmaceutical composition according to  claim 2 , wherein the binder is selected from the group consisting of hydroxypropylcellulose, hydroxypropyl methylcellulose, polyvinylpyrrolidone, and any mixture thereof. 
     
     
       19. The pharmaceutical composition according to  claim 3 , wherein the surface stabilizer is selected from the group consisting of sodium dodecyl sulfate, a water-soluble macromolecule compound, and any mixture thereof.